Gamma-butyrolactone (GBL) disruption of passive avoidance learning in the day-old chick appears to be due to its effect on GABAB not gamma-hydroxybutyric [corrected] acid (GHB) receptors.
Gamma-butyrolactone (GBL) is a prodrug to gamma-hydroxybutyric acid (GHB) and metabolises to GHB when ingested. Discrimination stimulus studies report generalisation of effects of GHB to GBL. While amnesia is one of the most commonly reported symptoms of GHB's ingestion in human users, as yet few studies have examined this effect. Although an endogenous GHB specific receptor is present in the brain, several studies have indicated that the clinical effects of exogenous doses of GBL/GHB are due to its action on GABA(B) receptors rather than on the GHB receptor. In this series of studies, New Hampshire x White leghorn cockerels were trained using a modified version of the passive avoidance learning task. Subcutaneous injections of GBL induced a memory deficit by 10 min post-training, which persisted for at least 24 h. No effect on memory was seen with administration of the specific GHB agonist NCS-356 (gamma-p-chlorophenyl-trans-4-hydroxycrotonate). The GBL-induced memory deficit appeared similar to the deficit produced by baclofen, where the antagonist facilitated learning. Additionally, GBL-induced memory deficit was ameliorated by application of a GABA(B) antagonist. The results support the hypothesis that GBL exerts its influence on memory via the GABA(B) receptor rather than by the specific GHB receptor.
Sherry
Joanne M
JM
School of Psychological Science, La Trobe University Bundoora, Bundoora 3086, Australia.
Hazi
Agnes
A
Hale
Mathew W
MW
Milsome
Sarah L
SL
Crowe
Simon F
SF
D015107:4-Butyrolactone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D002645:Chickens; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D007279:Injections, Subcutaneous; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D011956:Receptors, Cell Surface / Q000819:agonists*; D012997:Solvents / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
C039403:4-hydroxybutyric acid receptor; D018755:GABA Agonists; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D011956:Receptors, Cell Surface; D012997:Solvents; D001418:Baclofen; D015107:4-Butyrolactone